We have demonstrated the existence of marked alterations in immunological competence in two experimental models of diabetes mellitus: the C57B1/KsJ-db+/db+ mice and the streptozotocin-induced diabetic C57BL/6 mice. These studies, being performed under this proposal are the first comprehensive evaluation of immunological function in experimental diabetes. They should provide major insights into the functional consequences of the diabetic state on immunological reactivity and, additionally, should provide important insights into the hormonal regulation in immunological function. The objectives of this proposal are to extend our previous observations in two specific areas: 1. To demonstrate whether the alterations in immunological function which occur in experimental diabetes mellitus are a direct consequence of the abnormal in vivo metabolic milieu or whether they result from an intrinsic defect in the lymphoid cells themselves. 2. To further define the exact nature of the in vivo and in vitro immunological alterations occuring in diabetic mice.